Opus Genetics' VEGA-3 Trial Hits Primary Endpoint for Phentolamine 0.75% for Presbyopia

Phentolamine 0.75% improved near vision at 12 hours post-dose on Day 8.

Opus Genetics (North Carolina, United States) has announced that its pivotal VEGA-3 Phase III trial has successfully met its primary endpoint, confirming the potential of Phentolamine ophthalmic solution 0.75% as a novel treatment for presbyopia.

With both VEGA-2 and VEGA-3 trials meeting their primary endpoints, the company now has a strong foundation to move forward with FDA submission in the second half of 2025.

Opus Genetics announces the news on LinkedIn

VEGA-3: A closer look at the trial and its impact

Phentolamine ophthalmic solution 0.75% is a non-selective alpha-1 and alpha-2 adrenergic antagonist, designed to reduce pupil size by selectively blocking alpha-1 receptors in the radial iris dilator muscle—without affecting the ciliary muscle.

The VEGA-3 trial was a multicenter, randomized, double-masked, placebo-controlled Phase III study that enrolled 545 participants across 40 clinical sites in the United States. Patients were randomized in a 3:2 ratio to receive either Phentolamine ophthalmic solution 0.75% or placebo, administered once daily in the evening.

The primary endpoint was the percentage of participants achieving a ≥15-letter gain in binocular distance-corrected near visual acuity (DCNVA) with less than a 5-letter loss in binocular best-corrected distance visual acuity (BCDVA) at 12 hours post-dose on Day 8.

Here’s a breakdown of the results:

27.2% of patients receiving Phentolamine achieved a ≥15-letter gain in near visual acuity with less than a 5-letter loss in distance vision at 12 hours post-dose on Day 8, compared to 11.5% in the placebo group.
20.6% of Phentolamine users achieved the ≥15-letter gain at just 1-hour post-dose on Day 1 vs. 6.1% on placebo.
Patients also reported meaningful improvements in functional near vision, including satisfaction upon awakening and the ability to focus in low light.

“The results of the VEGA-3 trial reinforce our belief that Phentolamine Ophthalmic Solution 0.75% could offer an option to improve near vision for millions of adults affected by presbyopia,” said Dr. George Magrath, CEO, Opus Genetics.

Dr. Jay Pepose, Chief Medical Advisor at Opus Genetics, added: “These findings provide further validation of Phentolamine Ophthalmic Solution 0.75% as a differentiated approach to managing presbyopia, reflected by its ability to improve near vision while preserving distance vision without compromising low contrast vision.”

Safety profile

Phentolamine 0.75% also demonstrated a favorable safety profile, consistent with previous trials:

No treatment-related serious adverse events were reported.
Mild side effects included conjunctival hyperemia, instillation site irritation, dysgeusia (altered taste) and a low incidence of headache (2.6%).
No evidence of tachyphylaxis (loss of efficacy) was observed after six weeks.

Opus Genetics will continue to monitor the participants for long-term safety over 48 weeks.

Next steps: Toward regulatory review

Apart from the planned FDA submission in late 2025, Phentolamine Ophthalmic Solution 0.75% is also being evaluated in the LYNX clinical program for the treatment of dim-light vision disturbances following keratorefractive surgery.

While further regulatory steps remain, the VEGA-3 findings offer encouraging evidence that pharmacological treatments like Phentolamine could play a role in expanding options for patients with presbyopia. If approved, it could offer a non-invasive alternative for those seeking better near vision without compromising distance clarity.

Editor’s Note: See the full Opus Genetics press release. Additional information on the VEGA-3 trial is available at ClinicalTrials.gov (NCT06542497). This content is intended exclusively for healthcare professionals. It is not intended for the general public. Products or therapies discussed may not be registered or approved in all jurisdictions, including Singapore.